Preparation, antiangiogenic and antitumoral activities of the chemically sulfated glucan from Phellinus ribis

• The paper reported preparation of the sulfated derivatives of a β-glucan, which was isolated from Phellinus ribis for the first time.
• The sulfated derivatives had high antitumor activities in vivo, without producing any overt signs of general toxicity.
• The derivatives showed antiangiogenic activities in zebrafishes, as well as in H22 hepatoma in mice.
• It is possible to expect that the antitumoral effects of the sulfated derivatives are mediated via their antiangiogenic properties.

Two sulfated derivatives (PRP-S1 and PRP-S2) of a β-glucan from Phellinus ribis with different degrees of substitution were obtained by chlorosulfonic acid method. The derivatives could block formation of new vessels in zebrafish and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs). The two sulfated derivatives had remarkably high antitumor activities in vivo (in BALB/c mice inoculated with H22 hepatocellular carcinoma) as well as in vitro (against human ovary cancer SKOV-3 cells), without producing any overt signs of general toxicity. The results of immunohistochemistry assay indicated that the derivatives significantly reduced the average number of microvessel density (MVD) and inhibited the expression of vascular endothelial growth factor (VEGF) in tumor. Thus, these derivatives exhibit pronounced antiangiogenic and antitumoral properties. Except for cytotoxic effects on tumor cells, it is reasonable to expect that the antitumoral effects of PRP-S1 and PRP-S2 are mediated via their antiangiogenic properties.